Recombinant activated factor VII for intractable bleeding post splenectomy in a patient with myeloproliferative disorder.

Recombinant activated factor VII has been Food and Drug Administration approved to treat hemorrhages in hemophiliac patients with inhibitors and in acquired hemophilia patients. Recombinant activated factor VII use has also been considered for the management of uncontrolled bleeding in a number of congenital and acquired hemostatic abnormalities. The myeloproliferative disorders are a group of clonal hematologic diseases where, frequently, abnormal platelet function is considered a hallmark. This is the first case report addressing the clinical benefit of off-label use of recombinant activated factor VII in an attempt to control intractable bleeding in a patient with a myeloproliferative disorder after splenectomy.     

Recombinant activated factor VII for non-hemophiliac bleeding patients

THE PURPOSE OF THIS REVIEW: The purpose of this review is to summarize the safety and efficacy of recombinant activated factor VII in diverse clinical settings based on recent published anecdotal experiences and early results from prospective trials. RECENT FINDINGS: Recombinant activated factor VII is increasingly being used for off-label treatment and prophylaxis of bleeding in non-hemophiliac patients. Case reports would suggest that recombinant activated factor VII is an efficacious and safe "universal hemostatic agent". To date, results of several randomized control trials investigating recombinant activated factor VII in non-hemophiliacs have been published as abstracts, supporting recombinant activated factor VII safety, but not its efficacy. SUMMARY: Until the results of additional prospective trials are available, clinicians, who manage patients with challenging hemostatic complications, and transfusion medicine specialists should collaborate to develop local policies for off-label utilization of recombinant activated factor VII.     

Recombinant activated factor VII combined with desmopressin in preventing bleeding from dental extraction in a patient with Glanzmann's thrombasthenia.

The case of a 41-year-old woman with Glanzmann's thrombasthenia who underwent double dental extraction is presented. In the past, treatments with desmopressin (DDAVP) and tranexamic acid had often unsuccessful efficacy to stop or decrease bleeding. After ineffective DDAVP administration, the removal was performed successfully with recombinant activated factor VII (rFVIIa) infusion. rFVIIa infusion after DDAVP administration could be useful in patients with Glanzmann's thrombasthenia in which DDAVP and tranexamic acid weren't always effective.     

Recombinant activated factor VII in patients at high risk of bleeding

Currently, recombinant activated factor VII (rFVIIa) (NovoSeven) is indicated for the treatment of spontaneous and surgical bleeding in congenital haemophilia A and B patients with inhibitors to factors VIII (FVIII) and IX (FIX) >5 Bethesda units (BU) worldwide, and in patients with acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia in Europe. Until April 2003, almost three-quarters of a milion doses of rFVIIa have been administered proving its efficacy and excellent safety record. According to results from initial clinical trials and a large number of case reports, the rFVIIa may be effective not only in treating haemophilia patients but also in treatment of bleeding in patients on oral anticoagulation or heparin, patients with liver diseases, von Willebrand disease (vWD), thrombocytopenia, various platelet defects, congenital or acquired deficiency of FVII, and in subjects without any pre-existing coagulopathy with diffuse life-threatening bleeding triggered by surgery or trauma. This review will briefly summarize rFVIIa mode of action in haemostasis, the current clinical experience with rFVIIa and focus on the alternative use of rFVIIa in patients at the high risk of bleeding in both spontaneous cases and clinical trials reports.     

Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER

Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 μg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.     

Treatment of massive cecal bleeding in a 28-Year-old patient with homozygous factor V deficiency with activated factor VII

Factor V deficiency is usually accompanied with recurrent epistaxis, menorrhagia and haemorrhages after trauma. So far, gastrointestinal bleeding has not been reported. We describe here the first case of severe cecal bleeding in a 28-year-old woman with homozygous factor V deficiency. As a reasonable alternative to large amounts of fresh frozen plasma, we indicated recombinant activated factor VII (rFVIIa), as supra-physiological concentrations directly activate factor X and prothrombin on the surface of activated platelets. With this regimen, the bleeding immediately stopped and the patient was discharged three days later. Rotation thromboelastometry studies showed a marked improvement in clot generation after rFVIIa infusion. We conclude that massive cecal mucosal bleeding is a possible manifestation of homozygous factor V deficiency and rFVIIa could be a successful therapy.     

Recombinant activated factor VII for severe uterine bleeding after chemotherapy in a woman with acute myeloid leukemia.

Acute hemorrhage is sometimes a serious complication that may arise in patients with acute leukemia as a result of therapy-induced myelosuppression. In most cases, transfusion of platelets and red blood cells are used to manage this clinical entity. These therapeutic interventions are not always successful and a more direct approach to activating the coagulation system can be more effective and, in some instances, life saving. Recombinant activated factor VII (rFVIIa), which is used for management of hemophiliac patients with inhibitors, is a major alternative in such situations. Here we describe the use of rFVIIa in a 41-year-old patient with ongoing vaginal bleeding with acute myeloid leukemia. Our experience indicates that rFVIIa may be an effective salvage treatment in bleeding conditions related to leukemia.     

Continuous infusion of recombinant activated factor VII during caesarean section delivery in a patient with congenital factor VII deficiency

Recombinant activated factor VII (rFVIIa) can be used as an alternative therapy in patients with FVII deficiency. However, as the drug has a very short half-life, continuous infusion could be a meaningful administration modality. We report the case of a 30-year-old woman with moderate FVII deficiency and human immunodeficiency virus infection who underwent a caesarean section delivery. She was treated with a continuous infusion of rFVIIa and did not suffer any bleeding complication. The continuous infusion of rFVIIa was a safe and effective therapeutic approach for our patient, maintaining her levels of FVII:C and avoiding bleeding during caesarean section and afterwards.     

Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in patients with cirrhosis during bleeding from oesophageal varices

BACKGROUND: Patients with cirrhosis have low levels of coagulation factors, the most pronounced deficiency being that of FVII. This may compromise haemostasis during bleeding from ruptured oesophageal varices. The objective of this trial was to evaluate the effect of rFVIIa on prothrombin time in cirrhosis patients with ongoing variceal bleeding. Safety, including signs of DIC, was monitored. METHODS: The study is a single centre, open-label trial. Ten consecutive patients with known alcoholic cirrhosis and oesophageal variceal bleeding were included. The patients received routine treatment, including Terlipressin. Each patient received one i.v. injection of rFVIIa (80 microg/kg bw). The study observation time was 12 h per patient. RESULTS: The mean age of the patients was 48 years (8 men and 2 women). The cirrhosis was classified as Child B in 5 patients and Child C in 5. At baseline, all patients had prothrombin time levels above the normal range, and all but one had FVII coagulation activity (FVII:C) levels below the normal range. rFVIIa normalized the prothrombin time in all patients within 30 min. The effect lasted for more than 4 h in 7 patients, and for about 2 h in the remaining 3 patients. Immediate bleeding control was obtained in all patients, and no patient died within the study time. There was no sign of DIC. CONCLUSIONS: rFVIIa is effective in transiently reversing the prolonged prothrombin time in cirrhosis patients with haematemesis from varices. This indicates a potential of improving haemostasis and survival in patients with compromised coagulation due to liver disease.     

Acquired bleeding disorder in a patient with congenital factor VII deficiency

Clinical conference held at the Leiden University Hospital. Members of the Department of Hematology participated jointly in this conference. R. Bieger is the editor of this feature.     

Recombinant factor VIIa prophylaxis in a patient with severe congenital factor VII deficiency

Use of recombinant factor VIIa (rFVIIa, NovoSeven in patients with congenital FVII deficiency has been reported for the prophylactic management of surgical bleeding and for the treatment of acute bleeding episodes. Because of its short half-life, the use of rFVIIa on a regular prophylactic regimen has not been routinely adopted. In this report, we describe our successful experience with rFVIIa prophylaxis in preventing recurrent target joint bleeding in a severely FVII-deficient adolescent.